The Molecular Toxicology Research Core is led by Dr. James Yager and comprises investigators whose research focuses on fundamental mechanisms of toxicity of endogenous and environmental chemicals associated with human disease, particularly but not exclusively in an urban setting. These investigators number 14 and come from four departments in two schools. One of the major foci is on oxidative stress and damage, and projects range from approaches to identify genes important in reactive oxygen species (ROS) homeostasis in yeast to the adverse effects of ROS on DNA and regulation in mammalian cells. Another area is the characterization of genes important in the metabolism of environmental and endogenous chemicals, such as those encoding for P450 CYP1B1, which has estrogen-4-hydroxylase activity and can activate procarcinogens. Still other studies focus on lead neurotoxicity (the Neurotoxicology Research Core present in the previous proposal has been eliminated and a few of the former members included in this subsection). Lead focus areas include investigations of signal transduction via NMDA and cholinergic receptors, protein kinase C, cellular lead transport, and correlations of neurochemical effects with those on learning and memory. Still other faculty investigate signal transduction arising from estrogen and androgen receptors, which have potential importance in certain cancers and in aging of reproductive tissues. Numerous established, recent and planned collaborations within the Molecular Toxicology Core have been facilitated by the Center through support of the research core itself and the pilot project program and facility cores, especially the Molecular Biology, Cell and Tissue Analysis and Analytical Instrumentation Cores. The pilot project program has helped to develop the research programs of new faculty (e.g., Drs. Culotta and Sutter) and established faculty to move in new directions (e.g., Drs. Guilarte and Yager) that have led to successful extramural grant applications.